A Bioinspired\nCu<sup>2+</sup>-Responsive Magnetic\nResonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity

Imaging extracellular Cu<sup>2+</sup> in vivo is of paramount\ninterest\ndue to its biological importance in both physiological and pathological\nstates. Magnetic resonance imaging (MRI) is a powerful technique to\ndo so. However, the development of efficient MRI contrast agents selective\nfor Cu<sup>2+</sup>, particularly versus the more abundant Zn<sup>2+</sup> ions, is highly challenging. We present here an innovative\nCu<sup>2+</sup>-responsive MRI contrast agent that contains a bioinspired\nCu<sup>2+</sup> binding site. This sensor shows a remarkable increase\nin relaxivity of nearly 400% in the presence of Cu<sup>2+</sup>, which\ncould be rationalized in terms of an increase in the hydration number\nof the Ln<sup>3+</sup> ion, as demonstrated by spectroscopic and relaxometric\nstudies and supported by density functional theory calculations. Importantly,\nthe system also shows an unprecedented selectivity for Cu<sup>2+</sup>, in particular over Zn<sup>2+</sup>. Phantom MRI images were recorded\nat 9.4 T to highlight the potential of such probes, which lies directly\nin their bioinspired design.